Fluidic device with fluid port orthogonal to functionalized active region

ABSTRACT

A fluidic device includes at least one bulk acoustic wave (BAW) resonator structure with a functionalized active region, and at least one first (inlet) port defined through a cover structure arranged over a fluidic passage containing the active region. At least a portion of the at least one inlet port is registered with the active region, permitting fluid to be introduced in a direction orthogonal to a surface of the active region bearing functionalization material. Such arrangement promotes mixing proximate to a BAW resonator structure surface, thereby reducing analyte stratification, increasing analyte binding rate, and reducing measurement time.

STATEMENT OF RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.15/341,330, filed Nov. 2, 2016, now U.S. Pat. No. 10,533,972, whichclaims the benefit of provisional patent application Ser. No.62/249,515, filed Nov. 2, 2015, the disclosures of which are herebyincorporated herein by reference in their entireties.

TECHNICAL FIELD

The present disclosure relates to fluidic devices incorporating acousticresonators, including fluidic devices suitable for biosensing orbiochemical sensing applications.

BACKGROUND

A biosensor (or biological sensor) is an analytical device including abiological element and a transducer that converts a biological responseinto an electrical signal. Certain biosensors involve a selectivebiochemical reaction between a specific binding material (e.g., anantibody, a receptor, a ligand, etc.) and a target species (e.g.,molecule, protein, DNA, virus, bacteria, etc.), and the product of thishighly specific reaction is converted into a measurable quantity by atransducer. Other sensors may utilize a non-specific binding materialcapable of binding multiple types or classes of molecules or othermoieties that may be present in a sample, such as may be useful inchemical sensing applications. The term “functionalization material” maybe used herein to generally relate to both specific and non-specificbinding materials. Transduction methods used with biosensors may bebased on various principles, such as electrochemical, optical,electrical, acoustic, and so on. Among these, acoustic transductionoffers a number of potential advantages, such as being real time,label-free, and low cost, as well as exhibiting high sensitivity.

An acoustic wave device employs an acoustic wave that propagates throughor on the surface of a piezoelectric material, whereby any changes tothe characteristics of the propagation path affect the velocity and/oramplitude of the wave. Presence of functionalization material embodiedin a specific binding material along an active region of an acousticwave device permits a specific analyte to be bound to thefunctionalization material, thereby altering the mass being vibrated bythe acoustic wave and altering the wave propagation characteristics(e.g., velocity, thereby altering resonance frequency). Changes invelocity can be monitored by measuring the frequency,amplitude-magnitude, or phase characteristics of the acoustic wavedevice and can be correlated to a physical quantity being measured.

In the case of a piezoelectric crystal resonator, an acoustic wave mayembody a bulk acoustic wave (BAW) propagating through the interior (or“bulk”) of a substrate, or a surface acoustic wave (SAW) propagating onthe surface of the substrate. SAW devices involve transduction ofacoustic waves (commonly including two-dimensional Rayleigh waves)utilizing interdigital transducers along the surface of a piezoelectricmaterial, with the waves being confined to a penetration depth of aboutone wavelength. BAW devices typically involve transduction of anacoustic wave using electrodes arranged on opposing top and bottomsurfaces of a piezoelectric material. In a BAW device, three wave modescan propagate, namely, one longitudinal mode (embodying longitudinalwaves, also called compressional/extensional waves, and two shear modes(embodying shear waves, also called transverse waves), with longitudinaland shear modes respectively identifying vibrations where particlemotion is parallel to or perpendicular to the direction of wavepropagation. The longitudinal mode is characterized by compression andelongation in the direction of the propagation, whereas the shear modesconsist of motion perpendicular to the direction of propagation with nolocal change of volume. Longitudinal and shear modes propagate atdifferent velocities. In practice, these modes are not necessarily puremodes, as the particle vibration, or polarization, is neither purelyparallel nor purely perpendicular to the propagation direction. Thepropagation characteristics of the respective modes depend on thematerial properties and propagation direction respective to the crystalaxis orientations. Since shear waves exhibit a very low penetrationdepth into a liquid, a device with pure or predominant shear modes canoperate in liquids without significant radiation losses (in contrastwith longitudinal waves, which can be radiated in liquid and exhibitsignificant propagation losses). The ability to create sheardisplacements is beneficial for operation of acoustic wave devices withfluids (e.g., liquids) because shear waves do not impart significantenergy into fluids.

Certain piezoelectric thin films are capable of exciting bothlongitudinal and shear mode resonance, such as hexagonal crystalstructure piezoelectric materials including (but not limited to)aluminum nitride [AlN] and zinc oxide [ZnO]. To excite a wave includinga shear mode using a piezoelectric material arranged between electrodes,a polarization axis in a piezoelectric thin film must generally benon-perpendicular to (e.g., tilted relative to) the film plane. Inbiological sensing applications involving liquid media, the shearcomponent of the resonator is used. In such applications, piezoelectricmaterial may be grown with a c-axis orientation distribution that isnon-perpendicular relative to a face of an underlying substrate toenable a BAW resonator structure to exhibit a dominant shear responseupon application of an alternating current signal across electrodesthereof. Conversely, a piezoelectric material grown with a c-axisorientation that is perpendicular relative to a face of an underlyingsubstrate will enable a BAW resonator structure to exhibit a dominantlongitudinal response upon application of an alternating current signalacross electrodes thereof.

Typically, BAW devices are fabricated by micro-electro-mechanicalsystems (MEMS) fabrication techniques, owing to the need to providemicroscale features suitable for facilitating high-frequency operation.In the context of biosensors, functionalization materials (e.g.,specific binding materials; also known as bioactive probes or agents)may be deposited on sensor surfaces by microarray spotting (also knownas microarray printing) using a microarray spotting needle.Functionalization materials providing non-specific binding utility(e.g., permitting binding of multiple types or species of molecules) mayalso be used in certain contexts, such as chemical sensing.

Under typical operating conditions, flows in microfluidic passages orchannels (also termed “microchannels”) are laminar. Fluids in laminarflow tend to follow parallel streamline paths, such that the chaoticfluctuations of velocity that tend to homogenize fluids in turbulentflows are absent. Multiple fluids introduced in a standard microchannelgenerally will not mix with each other, except at a common interfacebetween the fluids via diffusion, and the diffusion process is typicallyslow in comparison to the flow of fluid along a principal axis of amicrofluidic channel. The same principles that inhibit rapid mixing offluids flowing under laminar conditions in a microfluidic channel alsoaffect the distribution of analytes contained in one or more fluidsflowing within a microfluidic channel. Flux moves from regions of highconcentration to regions of low concentration according to Fick's firstlaw of diffusion; additionally, the flux rate is proportional to theconcentration gradient difference. A hypothetical volume of fluidcontaining an analyte and advancing in a horizontal direction through amicrofluidic channel having functionalization material arranged along abottom surface of the channel may be modeled as a moving “stack” ofhorizontal fluid layers. Following passage in a horizontal directionover the functionalization material, a lowermost fluid layer of thestack will exhibit reduced or depleted analyte concentration due tobinding of analyte with the functionalization material. But sincediffusion is slow in a direction perpendicular to the direction of fluidflow through the microfluidic channel, and analyte needs to diffuse to asurface bearing functionalization material to bind, analyte present influid layers other than the lowermost fluid layer may not be availablefor binding with the functionalization material along the bottom surfaceof the channel within a reasonable period of time. Analyte concentrationmay remain stratified or inconsistently distributed within the channeluntil diffusion occurs. Additionally, large analyte molecules mayrequire a long time to bind with functionalization material. Due tothese considerations, analyte binding rate is limited, and an extendedtime may be necessary to complete measurement of a particular sample.

Accordingly, there is a need for fluidic devices incorporating bulkacoustic wave resonator structures, such as for biosensing orbiochemical sensing applications, that overcome limitations associatedwith conventional devices.

SUMMARY

The present disclosure relates to a fluidic device including at leastone bulk acoustic wave (BAW) resonator structure with a functionalizedactive region, and including at least one first port (e.g., inlet port)defined through a cover structure arranged over a fluidic passagecontaining the active region, wherein at least a portion of the at leastone first port is registered with the active region. Such arrangementpermits fluid to be introduced in a direction orthogonal to a surface ofthe active region that bears a functionalization material. Theorthogonal fluid flow promotes mixing proximate to the functionalizedactive region, thereby increasing binding of analyte and reducingmeasurement time. One or more layers (e.g., a hermeticity layer, aninterface layer, and/or a self-assembled monolayer) may be arrangedbetween the top side electrode and the functionalization material. Atleast one second port (e.g., outlet port) may be provided in variousconfigurations. Methods for biological or chemical sensing are furtherprovided.

In one aspect, a fluidic device includes: a base structure comprising:(i) a substrate; (ii) at least one bulk acoustic wave resonatorstructure supported by the substrate, the at least one bulk acousticwave resonator structure including a piezoelectric material, a top sideelectrode arranged over a portion of the piezoelectric material, and abottom side electrode arranged below at least a portion of thepiezoelectric material, wherein a portion of the piezoelectric materialis arranged between the top side electrode and the bottom side electrodeto form an active region; and (iii) at least one functionalizationmaterial arranged over at least a portion of the active region; a wallstructure arranged over at least a portion of the base structure anddefining lateral boundaries of a fluidic passage arranged to receive afluid and containing the active region; and a cover structure arrangedover the wall structure and defining an upper boundary of the fluidicpassage; wherein the cover structure defines at least one first portthat is in fluid communication with the fluidic passage, and at least aportion of the at least one first port is registered with the activeregion.

In certain embodiments, the wall structure and the cover structure areembodied in a monolithic body structure. In certain embodiments, thewall structure and the base structure are embodied in a monolithic bodystructure. In certain embodiments, the cover structure comprises a coverlayer, the wall structure comprises at least one wall layer, and the atleast one wall layer is arranged between the base structure and thecover layer.

In certain embodiments, the fluidic device further includes at least onesecond port that is in fluid communication with the fluidic passage,wherein the at least one second port is defined through the basestructure. In certain embodiments, the fluidic device further includesat least one second port that is in fluid communication with the fluidicpassage, wherein the at least one second port is defined through thewall structure. In certain embodiments, the fluidic device furtherincludes at least one second port that is in fluid communication withthe fluidic passage, wherein the at least one second port is definedthrough the cover structure.

In certain embodiments, the fluidic device further includes a pluralityof second ports in fluid communication with the fluidic passage, whereineach second port of the plurality of second ports is laterally displacedrelative to the at least one first port.

In certain embodiments, the at least one bulk acoustic wave resonatorstructure comprises a plurality of bulk acoustic wave resonatorstructures. In certain embodiments, the plurality of bulk acoustic waveresonator structures is registered with the fluidic passage.

In certain embodiments, the base structure further comprises at leastone acoustic reflector element arranged between the substrate and the atleast one bulk acoustic wave resonator structure.

In certain embodiments, the substrate defines a recess arranged belowthe active region.

In certain embodiments, the piezoelectric material comprises a c-axishaving an orientation distribution that is predominantly non-parallel tonormal of a face of the substrate.

In certain embodiments, the at least one functionalization materialcomprises a specific binding material. In certain embodiments, the atleast one functionalization material comprises a non-specific bindingmaterial.

In certain embodiments, the fluidic device further includes aself-assembled monolayer arranged between the at least onefunctionalization material and the top side electrode. In certainembodiments, the fluidic device further includes an interface layerarranged between the self-assembled monolayer and the top sideelectrode. In certain embodiments, the fluidic device further includes ahermeticity layer arranged between the interface layer and the top sideelectrode.

In another aspect, a method for biological or chemical sensing includes:supplying a fluid containing a target species to a fluidic deviceincluding a fluidic passage containing an active region of at least onebulk acoustic wave resonator structure, wherein at least a portion ofthe active region is overlaid with at least one functionalizationmaterial, wherein said supplying is configured to introduce the fluidthrough at least one first port registered with the active region tocause the fluid to enter the fluidic passage in a first direction normalto a planar surface of the active region and to cause at least some ofthe target species to bind to the at least one functionalizationmaterial; inducing a bulk acoustic wave in the active region; andsensing a change in at least one of an amplitude-magnitude property, afrequency property, or a phase property of the at least one bulkacoustic wave resonator structure to indicate at least one of presenceor quantity of target species bound to the at least onefunctionalization material.

In certain embodiments, the fluidic passage is in fluid communicationwith at least one second port that is laterally displaced relative tothe at least one first port, and said supplying is further configured tocause at least a portion of the fluid to transit through the fluidicpassage in a lateral direction and thereafter exit the fluidic passagethrough the at least one second port.

In certain embodiments, the at least one bulk acoustic wave resonatorstructure includes a top side electrode, a piezoelectric material, and abottom side electrode arranged over a substrate; the piezoelectricmaterial comprises a c-axis having an orientation distribution that ispredominantly non-parallel to normal of a face of the substrate; aportion of the piezoelectric material is arranged between the top sideelectrode and the bottom side electrode to form the active region; andthe inducing of a bulk acoustic wave in the active region comprisesapplying an alternating current signal across the top side electrode andthe bottom side electrode, whereby the at least one bulk acoustic waveresonator structure exhibits a dominant shear response upon applicationof the alternating current signal.

In another aspect, any of the foregoing aspects, and/or various separateaspects and features as described herein, may be combined for additionaladvantage. Any of the various features and elements as disclosed hereinmay be combined with one or more other disclosed features and elementsunless indicated to the contrary herein.

Those skilled in the art will appreciate the scope of the presentdisclosure and realize additional aspects thereof after reading thefollowing detailed description of the preferred embodiments inassociation with the accompanying drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawing figures incorporated in and forming a part ofthis specification illustrate several aspects of the disclosure, andtogether with the description serve to explain the principles of thedisclosure.

FIG. 1 is a schematic cross-sectional view of a portion of a bulkacoustic wave (BAW) MEMS resonator device usable with embodimentsdisclosed herein, including an active region with a piezoelectricmaterial arranged between overlapping portions of a top side electrodeand a bottom side electrode.

FIG. 2 is a schematic cross-sectional view of an upper portion of a BAWMEMS resonator device including a piezoelectric material and a top sideelectrode overlaid with a hermeticity layer, an interface layer, aself-assembled monolayer, and a functionalization (e.g., specificbinding) material.

FIG. 3 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by a BAW resonator structure, bounded laterally bywalls, and bounded from above by a cover or cap layer, with aself-assembled monolayer (SAM) arranged over the entire piezoelectricmaterial and blocking material arranged over portions of the SAMnon-coincident with an active region distal from fluidic ports definedin the cover or cap layer, to serve as a first comparison deviceintended to provide context for subsequently described embodiments ofthe disclosure.

FIG. 4 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by a BAW resonator structure, bounded laterally bywalls, and bounded from above by a cover or cap layer, with an interfacelayer, a SAM, and functionalization material arranged only over anactive region distal from fluidic ports defined in the cover or caplayer, to serve as a second comparison device intended to providecontext for subsequently described embodiments of the disclosure.

FIG. 5 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by a BAW resonator structure, bounded laterally bywalls, and bounded from above by a cover or cap layer defining an inletport and two outlet ports, with a SAM and functionalization materialarranged over an active region, with the inlet port arranged above theactive region, and with the outlet ports being laterally displaced fromthe active region.

FIG. 6 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by a BAW resonator structure, bounded laterally bywalls, and bounded from above by a cover or cap layer defining an inletport, with a SAM and functionalization material arranged over an activeregion, with the inlet port arranged above the active region, and withtwo outlet ports defined in the BAW resonator structure.

FIG. 7 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by a BAW resonator structure, bounded laterally bywalls, and bounded from above by a cover or cap layer defining multipleinlet ports and multiple outlet ports, with a SAM and functionalizationmaterial arranged over an active region, and with the inlet ports and atleast some outlet ports arranged over the active region.

FIG. 8A is a schematic cross-sectional view of a film bulk acoustic waveresonator (FBAR) structure usable in devices according to certainembodiments, with the FBAR structure including an inclined c-axishexagonal crystal structure piezoelectric material, a substrate defininga cavity covered by an optional support layer, and an active regionregistered with the cavity, with a portion of the piezoelectric materialarranged between overlapping portions of a top side electrode and abottom side electrode.

FIG. 8B is a schematic cross-sectional view of the FBAR structure ofFIG. 8A with two outlet ports defined through the FBAR structure andlaterally offset from the active region.

FIG. 8C is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by the FBAR structure of FIG. 8B, bounded laterallyby walls, and bounded from above by a cover or cap layer defining aninlet port, with a SAM and functionalization material arranged over anactive region, and with the inlet port being arranged over the activeregion.

FIG. 9 is a top plan view photograph of a bulk acoustic wave MEMSresonator device suitable for receiving a hermeticity layer, aninterface layer, a self-assembled monolayer, and functionalization (e.g.specific binding) material as disclosed herein.

FIG. 10 is a perspective assembly view of a microfluidic deviceincorporating a substrate with multiple bulk acoustic wave MEMSresonator devices as disclosed herein, an intermediate layer defining achannel containing active regions of the MEMS resonator devices, and acover or cap layer defining multiple inlet ports arranged above theactive regions and defining multiple outlet ports laterally displacedfrom the active regions.

FIG. 11 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) including a fluidic passagebounded from below by a BAW resonator structure, bounded laterally bywalls, and bounded from above by a cover or cap layer defining an inletport, with a SAM and functionalization material arranged over an activeregion, with the inlet port arranged above the active region, and withtwo outlet ports defined in the BAW resonator structure, oralternatively defined in the wall structure as shown with dotted lines.FIG. 11 is essentially the same as FIG. 6 except that the cover andwalls are shown as monolithic in FIG. 11.

DETAILED DESCRIPTION

The embodiments set forth below represent the necessary information toenable those skilled in the art to practice the embodiments andillustrate the best mode of practicing the embodiments. Upon reading thefollowing description in light of the accompanying drawing figures,those skilled in the art will understand the concepts of the disclosureand will recognize applications of these concepts not particularlyaddressed herein. It should be understood that these concepts andapplications fall within the scope of the disclosure and theaccompanying claims.

It should be understood that, although the terms first, second, etc. maybe used herein to describe various elements, these elements should notbe limited by these terms. These terms are only used to distinguish oneelement from another. For example, a first element could be termed asecond element, and, similarly, a second element could be termed a firstelement, without departing from the scope of the present disclosure. Asused herein, the term “and/or” includes any and all combinations of oneor more of the associated listed items.

It should also be understood that when an element is referred to asbeing “connected” or “coupled” to another element, it can be directlyconnected or coupled to the other element or intervening elements may bepresent. In contrast, when an element is referred to as being “directlyconnected” or “directly coupled” to another element, there are nointervening elements present.

It should be understood that, although the terms “upper,” “lower,”“bottom,” “intermediate,” “middle,” “top,” and the like may be usedherein to describe various elements, these elements should not belimited by these terms. These terms are only used to distinguish oneelement from another. For example, a first element could be termed an“upper” element and, similarly, a second element could be termed an“upper” element depending on the relative orientations of theseelements, without departing from the scope of the present disclosure.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the disclosure.As used herein, the singular forms “a,” “an,” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises,”“comprising,” “includes,” and/or “including” when used herein specifythe presence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this disclosure belongs. It willbe further understood that terms used herein should be interpreted ashaving meanings that are consistent with their meanings in the contextof this specification and the relevant art and will not be interpretedin an idealized or overly formal sense unless expressly so definedherein.

The present disclosure relates to a fluidic device including at leastone bulk acoustic wave (BAW) resonator structure with a functionalizedactive region, and including at least one first port (e.g., inlet port)defined through a cover structure arranged over a fluidic passagecontaining the active region, wherein at least a portion of the at leastone first port is registered with the active region. Fluid is introducedin a direction orthogonal to a surface of the active region that bears afunctionalization material. Fluid flow changes direction proximate tothe active region (e.g., from a vertical direction to a lateraldirection) before traveling to at least one second port (e.g., outletport). This flow pattern promotes mixing proximate to the functionalizedactive region, thereby reducing stratification of analyte, increasingbinding of analyte, and reducing measurement time. One or more layers(e.g., a hermeticity layer, an interface layer, and/or a self-assembledmonolayer) may be arranged between the top side electrode and thefunctionalization material. The at least one second port (e.g., outletport) may be provided in various configurations. Methods for biologicalor chemical sensing are further provided.

To enable a change in flow direction, a functionalized surface of anactive region of a BAW resonator structure may be arranged in a fluidicpassage, whereby fluid is introduced through at least one first port(e.g., fluidic inlet port) into the fluidic passage, and the at leastone first port is arranged above and registered with the active region.In certain embodiments, the fluidic passage includes a width dimensionextending beyond a width of the active region. In certain embodiments,lateral boundaries of the fluidic passage are defined by a wallstructure arranged between a base structure (including a substrate andthe BAW resonator structure) and a cover structure. In certainembodiments, the wall structure and the cover structure are integratedand embodied in a monolithic body structure. In other embodiments, thewall structure and the base structure may be integrated and embodied ina monolithic body structure.

In certain embodiments, at least one first port is substantiallycentered relative to an active region. In certain embodiments, only aportion of the at least one first port is arranged directly over anactive region.

In certain embodiments, at least one first port comprises a widthdimension that exceeds a width dimension of an active region. In otherembodiments, the active region comprises a width dimension that exceedsa width dimension of the at least one first port. In either instance, atleast a portion of the at least one first port may be registered withthe active region.

In certain embodiments, at least one second port (e.g., fluidic outletport) may be defined though a cover structure (e.g., comprising a coverlayer). In certain embodiments, each fluidic outlet port may belaterally offset relative to an active region of a BAW resonatorstructure. In other embodiments, a portion of the at least one secondport may overlap a portion of the active region.

In certain embodiments, at least one second port (e.g., fluidic outletport) may be defined though a wall structure that is intermediatelyarranged between a cover structure and a base structure.

In certain embodiments, at least one second port (e.g., fluidic outletport) may be defined through a base structure, including through asubstrate and a piezoelectric material. In certain embodiments, at leastone first port and at least one second port may be defined through thesubstrate and piezoelectric material via laser micromachining guided ina water jet. Other hole-defining methods may be used, including but notlimited to etching or mechanical drilling.

In certain embodiments, multiple second ports may be provided to promotedivision or splitting of one or more fluid inlet flows to a largernumber of fluid outlet flows.

In certain embodiments, a BAW resonator structure comprises a hexagonalcrystal structure piezoelectric material (e.g., aluminum nitride or zincoxide) that includes a c-axis having an orientation distribution that isnon-parallel (and also non-perpendicular) to normal of a face of asubstrate over which the piezoelectric material is formed, therebyproviding a quasi-shear mode acoustic resonator. Such a c-axisorientation distribution enables creation of shear displacements atcertain frequencies (which beneficially enables operation of a BAWresonator-based sensing device in liquid environments), and enablescreation of longitudinal displacements at other frequencies (which maybe useful to promote localized mixing). Methods for forming hexagonalcrystal structure piezoelectric materials including a c-axis having anorientation distribution that is predominantly non-parallel to normal ofa face of a substrate are disclosed in U.S. Pat. No. 9,922,809, with theforegoing patent hereby being incorporated by reference herein.Additional methods for forming piezoelectric material having an inclinedc-axis orientation are disclosed in U.S. Pat. No. 4,640,756 issued onFeb. 3, 1987, with the foregoing patent hereby being incorporated byreference herein.

Before describing fluidic devices with inlet ports orthogonal tofunctionalized active regions, exemplary bulk acoustic wave MEMSresonator devices, associated layers useful for providing biochemicalsensing utility, and fluidic devices incorporating MEMS resonatordevices will be introduced.

Micro-electrical-mechanical system (MEMS) resonator devices according tocertain embodiments include a substrate, a BAW resonator structurearranged over at least a portion of the substrate, and afunctionalization material arranged over at least a portion of an activeregion of the BAW resonator structure. Various layers may be arrangedbetween the functionalization material and a top side electrode (whichis coincident with an active region of the BAW resonator structure),such as: a hermeticity layer (e.g., to protect the top side electrodefrom corrosion in a liquid environment), an interface layer, and/or aself-assembled monolayer (SAM), with the interface layer and/or the SAMbeing useful to facilitate attachment of at least one overlying materiallayer, ultimately including functionalization material. In certainembodiments, the interface layer facilitates attachment of an overlyingSAM, and the SAM facilitates attachment of an overlyingfunctionalization material. In certain embodiments, multiplefunctionalization materials may be provided.

FIG. 1 is a schematic cross-sectional view of a portion of a bulkacoustic wave (BAW) MEMS resonator device 10 useable with embodimentsdisclosed herein. The resonator device 10 includes a substrate 12 (e.g.,typically silicon or another semiconductor material), an acousticreflector 14 arranged over the substrate 12, a piezoelectric material22, and bottom and top side electrodes 20, 28. The bottom side electrode20 is arranged along a portion of a lower surface 24 of thepiezoelectric material 22 (between the acoustic reflector 14 and thepiezoelectric material 22), and the top side electrode 28 is arrangedalong a portion of an upper surface 26 of the piezoelectric material 22.An area in which the piezoelectric material 22 is arranged betweenoverlapping portions of the top side electrode 28 and the bottom sideelectrode 20 is considered an active region 30 of the resonator device10. The acoustic reflector 14 serves to reflect acoustic waves andtherefore reduce or avoid their dissipation in the substrate 12. Incertain embodiments, the acoustic reflector 14 includes alternating thinlayers 16, 18 of materials (e.g., silicon oxicarbide [SiOC], siliconnitride [Si₃N₄], silicon dioxide [SiO₂], aluminum nitride [AlN],tungsten [W], and molybdenum [Mo]) having different acoustic impedancevalues, optionally embodied in a quarter-wave Bragg mirror, depositedover the substrate 12. In certain embodiments, other types of acousticreflectors may be used. Steps for forming the resonator device 10 mayinclude depositing the acoustic reflector 14 over the substrate 12,followed by deposition of the bottom side electrode 20, followed bygrowth (e.g., via sputtering or other appropriate methods) of thepiezoelectric material 22, followed by deposition of the top sideelectrode 28.

In certain embodiments, the piezoelectric material 22 comprises ahexagonal crystal structure piezoelectric material (e.g., aluminumnitride or zinc oxide) that includes a c-axis having an orientationdistribution that is predominantly non-parallel to (and may also benon-perpendicular to) normal of a face of the substrate 12. Underappropriate conditions, presence of a c-axis having an orientationdistribution that is predominantly non-parallel to normal of a face of asubstrate enables a BAW resonator structure to be configured to exhibita dominant shear response upon application of an alternating currentsignal across a top side electrode and a bottom side electrode.

The bulk acoustic wave MEMS resonator device 10 shown in FIG. 1 lacksany layers (e.g., including functionalization material) overlying theactive region 30 that would permit the resonator device 10 to be used asa biochemical sensor. If desired, at least portions of the resonatordevice 10 shown in FIG. 1 (e.g., including the active region 30) may beoverlaid with various layers, such as one or more of: a hermeticitylayer, an interface layer, a self-assembled monolayer (SAM), and/or afunctionalization material (which may include specific binding materialor non-specific binding material).

FIG. 2 is a schematic cross-sectional view of an upper portion of a BAWMEMS resonator device including a piezoelectric material 22 and a topside electrode 28 overlaid with a hermeticity layer 32, an interfacelayer 34, a self-assembled monolayer (SAM) 36, and a functionalization(e.g., specific binding) material 38. In certain embodiments, one ormore blocking materials (not shown) may be applied during fabrication,such as over portions of the interface layer 34 to prevent localizedattachment of one or more subsequently deposited layers, or (if appliedover selected regions of the SAM 36 or functionalization material 38) toprevent analyte capture in regions not overlying the active region 30 ofthe BAW MEMS resonator device.

In certain embodiments, photolithography may be used to promotepatterning of interface material or blocking material over portions of aMEMS resonator device. Photolithography involves use of light totransfer a geometric pattern from a photomask to a light-sensitivechemical photoresist on a substrate and is a process well known to thoseof ordinary skill in the semiconductor fabrication art. Typical stepsemployed in photolithography include wafer cleaning, photoresistapplication (involving either positive or negative photoresist), maskalignment, and exposure and development. After features are defined inphotoresist on a desired surface, an interface layer may be patterned byetching in one or more gaps in a photoresist layer, and the photoresistlayer may be subsequently removed (e.g., by using a liquid photoresiststripper, by ashing via application of an oxygen-containing plasma, oranother removal process).

In certain embodiments, an interface layer (e.g., arrangeable between atop side electrode and a SAM) includes a hydroxylated oxide surfacesuitable for formation of an organosilane SAM. A preferred interfacelayer material including a hydroxylated oxide surface is silicon dioxide[SiO₂]. Alternative materials incorporating hydroxylated oxide surfacesfor forming interface layers include titanium dioxide [TiO₂], tantalumpentoxide [Ta₂O₅], hafnium oxide [HfO₂], or aluminum oxide [Al₂O₃].Other alternative materials incorporating hydroxylated oxide surfaceswill be known to those skilled in the art, and these alternatives areconsidered to be within the scope of the present disclosure.

In other embodiments, an interface layer (e.g., arrangeable between atop side electrode and a SAM), or at least one electrode that is devoidof an overlying interface layer, includes gold or another noble metal(e.g., ruthenium, rhodium, palladium, osmium, iridium, platinum, orsilver) suitable for receiving a thiol-based SAM that may be overlaidwith functionalization material.

In certain embodiments incorporating electrode materials subject tocorrosion, a hermeticity layer may be applied between a top sideelectrode and an interface layer. A hermeticity layer may be unnecessarywhen noble metals (e.g., gold, platinum, etc.) are used for top sideelectrodes. If provided, a hermeticity layer preferably includes adielectric material with a low water vapor transmission rate (e.g., nogreater than 0.1 g/m²/day). Following deposition of a hermeticity layerand an interface layer, a SAM may be formed over the interface layer,with the SAM including an organosilane material in certain embodiments.The hermeticity layer protects a reactive electrode material (e.g.,aluminum or aluminum alloy) from attack in corrosive liquidenvironments, and the interface layer facilitates proper chemicalbinding of the SAM.

In certain embodiments, a hermeticity layer and/or an interface layermay be applied via one or more deposition processes such as atomic layerdeposition (ALD), chemical vapor deposition (CVD), or physical vapordeposition (PVD). Of the foregoing processes, ALD is preferred fordeposition of at least the hermeticity layer (and may also be preferablefor deposition of the interface layer) due to its ability to provideexcellent conformal coating with good step coverage over device featuresso as to provide layer structures that are free of pinholes. Moreover,ALD is capable of forming uniformly thin layers that provide relativelylittle damping of acoustic vibrations that would otherwise result indegraded device performance. Adequacy of coverage is important for ahermeticity layer (if present) to avoid corrosion of the underlyingelectrode. If ALD is used for deposition of a hermeticity layer, then incertain embodiments a hermeticity layer may include a thickness in arange of from about 10 nm to about 25 nm. In certain embodiments,hermeticity layer thickness is about 15 nm, or from about 12 nm to about18 nm. Conversely, if another process such as chemical vapor depositionis used, then a hermeticity layer may include a thickness in a range offrom about 80 nm to about 150 nm or more, or in a range of from about 80nm to about 120 nm. Considering both of the foregoing processes,hermeticity layer thicknesses may range from about 5 nm to about 150 nm.If ALD is used for deposition of an interface layer, then an interfacelayer may include a thickness in a range of from about 5 nm to about 15nm. In certain embodiments, an interface layer may include a thicknessof about 10 nm, or in a range of from about 8 nm to about 12 nm. Otherinterface layer thickness ranges and/or deposition techniques other thanALD may be used in certain embodiments. In certain embodiments, ahermeticity layer and an interface layer may be sequentially applied ina vacuum environment, thereby promoting a high-quality interface betweenthe two layers.

If provided, a hermeticity layer may include an oxide, a nitride, or anoxynitride material serving as a dielectric material and having a lowwater vapor transmission rate (e.g., no greater than 0.1 g/m²/day)according to certain embodiments. In certain embodiments, a hermeticitylayer includes at least one of aluminum oxide [Al₂O₃] or silicon nitride[SiN]. In certain embodiments, an interface layer includes at least oneof SiO₂, TiO₂, or Ta₂O₅. In certain embodiments, multiple materials maybe combined in a single hermeticity layer, and/or a hermeticity layermay include multiple sublayers of different materials. Preferably, ahermeticity layer is further selected to promote compatibility with anunderlying reactive metal (e.g., aluminum or aluminum alloy) electrodestructure of an acoustic resonator structure. Although aluminum oraluminum alloys are frequently used as electrode materials in BAWresonator structures, various transition and post-transition metals canbe used for such electrodes.

Following deposition of an interface layer (optionally arranged over anunderlying hermeticity layer), a SAM is preferably formed over theinterface layer. SAMs are typically formed by exposure of a solidsurface to amphiphilic molecules with chemical groups that exhibitstrong affinities for the solid surface. When an interface layercomprising a hydroxylated oxide surface is used, then organosilane SAMsare particularly preferred for attachment to the hydroxylated oxidesurface. Organosilane SAMs promote surface bonding throughsilicon-oxygen (Si—O) bonds. More specifically, organosilane moleculesinclude a hydrolytically sensitive group and an organic group and aretherefore useful for coupling inorganic materials to organic polymers.An organosilane SAM may be formed by exposing a hydroxylated oxidesurface to an organosilane material in the presence of trace amounts ofwater to form intermediate silanol groups. These groups then react withfree hydroxyl groups on the hydroxylated oxide surface to covalentlyimmobilize the organosilane. Examples of possible organosilane-basedSAMs that are compatible with interface layers incorporatinghydroxylated oxide surfaces include 3-glycidoxypropyltrimethoxysilane(GPTMS), 3-mercaptopropyltrimethoxysilane (MPTMS),3-aminopropyltrimethoxysilane (APTMS), and octadecyltrimethoxysilane(OTMS), including their ethoxy- and chloro-variants. Additional silanesthat may be used for SAMs include poly(ethylene glycol) (PEG) conjugatedvariants. Those skilled in the art will recognize that otheralternatives exist, and these alternatives are considered to be withinthe scope of the present disclosure. An exemplary SAM may include athickness in a range of at least 0.5 nm or more. Preferably, a SAMreadily binds to the locally patterned interface layer but does notreadily bind to other adjacent material layers (e.g., a hermeticitylayer, a piezoelectric material, and/or a blocking material layer).

When an electrode and/or interface layer comprising gold or anothernoble metal is used, then thiol-based (e.g., alkanethiol-based) SAMs maybe used. Alkanethiols are molecules with an S—H head group, a tailgroup, and a back bone comprising an alkyl chain. Thiols may be used onnoble metal interface layers due to the strong affinity of sulfur forthese metals. Examples of thiol-based SAMs that may be used include, butare not limited to, 1-dodecanethiol (DDT), 11-mercaptoundecanoic acid(MUA), and hydroxyl-terminated (hexaethylene glycol) undecanethiol(1-UDT). These thiols contain the same backbone, but different endgroups—namely, methyl (CH₃), carboxyl (COOH), and hydroxyl-terminatedhexaethylene glycol (HO—(CH₂CH₂O)₆) for DDT, MUA, and 1-UDT,respectively. In certain embodiments, SAMs may be formed by incubatinggold surfaces in thiol solutions using a suitable solvent, such asanhydrous ethanol.

Following formation of a SAM, the SAM may be biologicallyfunctionalized, such as by receiving at least one functionalization(e.g., specific binding) material. In certain embodiments, specificbinding materials may be applied on or over a SAM using a microarrayspotting needle or other suitable methods. In certain embodiments, aninterface layer may be patterned (e.g., using photolithographic maskingand selective etching for defining the interface layer) with a highdimensional tolerance over only a portion of a BAW resonator structure(which includes a substrate), a SAM may be applied over the interfacelayer, and a subsequently applied specific binding material may beattached only to the SAM. In certain embodiments, patterning of aninterface layer may provide a higher dimensional tolerance forpositioning of the specific binding material than could be attained bymicroarray spotting alone. Examples of specific binding materialsinclude, but are not limited to, antibodies, receptors, ligands, and thelike. A specific binding material is preferably configured to receive apredefined target species (e.g., molecule, protein, DNA, virus,bacteria, etc.). A functionalization material including specific bindingmaterial may include a thickness in a range of from about 5 nm to about1000 nm, or from about 5 nm to about 500 nm. In certain embodiments, anarray of different specific binding materials may be provided overdifferent active areas of a multi-resonator structure (i.e., one or moreresonator structures including multiple active regions), optionally incombination with one or more active areas that are devoid of specificbinding materials to serve as comparison (or “reference”) regions. Incertain embodiments, a functionalization (e.g., bio-functionalization)material may provide non-specific binding utility.

Certain embodiments are directed to a fluidic device including multiplebulk acoustic wave (BAW) MEMS resonator structures as disclosed hereinand including a fluidic passage (e.g., a channel, a chamber, or thelike) arranged to conduct a liquid to contact at least onefunctionalization (e.g., specific binding) material arranged over atleast one active region of the BAW MEMS resonator structures. Such adevice may be microfluidic in scale, and may comprise at least onemicrofluidic passage (e.g., having at least one dimension, such asheight and/or width, of no greater than about 500 microns, or about 250microns, or about 100 microns). For example, following fabrication ofbulk acoustic wave MEMS resonator structures and deposition of a SAMover portions thereof (optionally preceded by deposition of ahermeticity layer and an interface layer), a microfluidic device may befabricated by forming one or more walls defining lateral boundaries of amicrofluidic passage over a first bulk acoustic wave MEMS resonatorstructure with an active region thereof arranged along a bottom surfaceof the microfluidic passage, and then enclosing the microfluidic passageusing a cover or cap layer that may define fluidic ports (e.g.,openings) enabling fluid communication with the microfluidic passage. Incertain embodiments, functionalization (e.g., specific binding) materialmay be pre-applied to the active region of a bulk acoustic wave MEMSresonator structure before formation of the microfluidic passage; inother embodiments, functionalization material may be applied over anactive region of a bulk acoustic wave resonator structure followingformation of the microfluidic passage.

Walls of a microfluidic passage may be formed of any suitable material,such as laser-cut “stencil” layers of thin polymeric materials and/orlaminates, optionally including one or more self-adhesive surfaces(e.g., adhesive tape). Optionally such walls may be formed prior todeposition of a SAM, functionalization material, and/or blocking layers,with an SU-8 negative epoxy resist or other photoresist material. Incertain embodiments, a cover or cap layer may be integrally formed withone or more walls (e.g., via molding or another suitable process) todefine a portion of an upper boundary as well as lateral boundaries ofat least one fluidic passage, and the integrally formed partialcover/wall structure may be applied (e.g., adhered or otherwise bonded)over at least a portion of a bulk acoustic wave resonator structure toenclose the at least one fluidic passage.

In certain embodiments, a chemical or biological blocking material maybe applied over a portion of a SAM to prevent attachment of afunctionalization (e.g., specific binding) material over one or moreselected regions of a BAW resonator structure (e.g., one or more regionsapart from an active region). The proper choice of a chemical orbiological blocking material (e.g., blocking buffer) for a givenanalysis depends on the type of target species or analyte present in asample. Various types of blocking buffers such as highly purifiedproteins, serum, or milk may be used to block free sites on a SAM.Additional blockers include ethanolamine or polyethylene oxide(PEO)-containing materials. An ideal blocking buffer would bind to allpotential sites of non-specific interaction away from an active region.To optimize a blocking buffer for a particular analysis, empiricaltesting may be used to determine signal-to-noise ratio. No singlechemical or biological blocking material is ideal for every situation,since each antibody-antigen pair has unique characteristics.

FIG. 3 is a schematic cross-sectional view of a portion of a fluidicdevice 56 (e.g., a biochemical sensor device) including a fluidicpassage 52 (which may be microfluidic in character) that is bounded frombelow by a bulk acoustic wave resonator structure including an activeregion 30, bounded laterally by walls 44, and bounded from above by acover or cap layer 46 defining a fluidic inlet port 48 and a fluidicoutlet port 50, with the fluidic device 56 serving as a first comparisondevice intended to provide context for subsequently describedembodiments of the disclosure. The fluidic device 56 includes asubstrate 12 overlaid with an acoustic reflector 14, and a bottom sideelectrode 20 arranged generally below a piezoelectric material 22. A topside electrode 28 extends over a portion of the piezoelectric material22, wherein a portion of the piezoelectric material 22 arranged betweenthe top side electrode 28 and the bottom side electrode 20 embodies theactive region 30 of the BAW resonator structure. The bottom sideelectrode 20 is arranged along a portion of a lower surface 24 of thepiezoelectric material 22. The top side electrode 28 and thepiezoelectric material 22 are overlaid with a hermeticity layer 32, aninterface layer 34, and a self-assembled monolayer (SAM) 36. Portions ofthe SAM 36 between the active region 30 and the walls 44 are overlaidwith a chemical or biological blocking material 54 to prevent localizedattachment of functionalization material and/or analyte. A portion ofthe SAM 36 that is registered with the active region 30 is overlaid witha layer of functionalization (e.g., specific binding) material 38arranged to bind at least one analyte. Walls 44 that are laterallydisplaced from the active region 30 extend upward from the SAM 36 todefine lateral boundaries of the fluidic passage 52 containing theactive region 30. The walls 44 may be formed of any suitable material,such as a laser-cut “stencil” layer of thin polymeric materials and/orlaminate materials, optionally including one or more self-adhesivesurfaces (e.g. adhesive tape). Optionally such walls 44 may be formedprior to deposition of the SAM 36, functionalization material 38, andchemical or biological blocking material 54 with an SU-8 negative epoxyresist or other photoresist material. The cover or cap layer 46 definingfluidic inlet and outlet ports 48, 50 is further provided to provide anupper boundary for the fluidic passage 52. The cover or cap layer 46 maybe formed by defining fluidic inlet and outlet ports 48, 50 (e.g., vialaser cutting or water jet cutting) in a layer of an appropriatematerial (e.g., a substantially inert polymer, glass, silicon, ceramic,or the like), and adhering the cover or cap layer 46 to top surfaces ofthe walls 44.

In use of the fluidic device 56, a fluid sample may be supplied throughthe fluidic inlet port 48 into the fluidic passage 52 over the activeregion 30 and then flow through the fluidic outlet port 50 to exit thefluidic passage 52. Due to the laminar nature of the fluid flow withinthe fluidic passage 52, the fluid volume may be modeled and behave as a“stack” of horizontal fluid layers including a lowermost fluid layer 40Aand an uppermost fluid layer 40N. An analyte 42 contained in thelowermost fluid layer 40A of the fluid sample will tend to bind withfunctionalization material 38 arranged over the active region 30.Analyte contained in fluid layers above the lowermost fluid layer 40A(including the uppermost fluid layer 40N) may not be available to bindwith the functionalization material 38, since diffusion of analyte(e.g., in a vertical direction) between the fluid layers 40A-40N mayoccur slowly. Assuming that sufficient analyte is present proximate tothe lowermost fluid layer 40A to bind with functionalization material 38arranged over the active region 30, when a bulk acoustic wave having adominant shear component is induced in the active region 30 by supplyingan electrical (e.g., alternating current) signal of a desired frequencyto the bottom and top side electrodes 20, 28, a change inelectroacoustic response (e.g., at least one of an amplitude-magnitudeproperty, a frequency property, or a phase property, such as a shift inresonant frequency) of the BAW resonator structure may be detected toindicate a presence and/or quantity of analyte bound to thefunctionalization material 38.

FIG. 4 is a schematic cross-sectional view of a portion of a fluidicdevice (e.g., a biochemical sensor device) 58 similar to the fluidicdevice 56 of FIG. 3, serving as a second comparison device intended toprovide context for subsequently described embodiments of thedisclosure. As compared to the fluidic device 56 of FIG. 3, the fluidicdevice 58 of FIG. 4 includes an interface layer 34 and a SAM 36 that areprovided solely over an active region 30 instead of over an entirety ofpiezoelectric material 22. Such configuration may be provided bycontrolling lateral boundaries of the interface layer 34 (e.g., byphotolithographic patterning and selective etching, for example). Thefluidic device 58 includes a fluidic passage 52 that is bounded frombelow by a bulk acoustic wave resonator structure including the activeregion 30, bounded laterally by walls 44, and bounded from above by acover or cap layer 46 defining a fluidic inlet port 48 and a fluidicoutlet port 50. The fluidic device 58 includes a substrate 12 overlaidwith an acoustic reflector 14, and a bottom side electrode 20 arrangedgenerally below the piezoelectric material 22. The bottom side electrode20 is arranged along a portion of a lower surface 24 of thepiezoelectric material 22. A top side electrode 28 extends over aportion of the piezoelectric material 22, wherein a portion of thepiezoelectric material 22 arranged between the top side electrode 28 andthe bottom side electrode 20 embodies the active region 30 of the BAWresonator structure. A hermeticity layer 32 is arranged over the topside electrode 28 and the piezoelectric material 22. The interface layer34 and the SAM 36 are provided over a portion of the hermeticity layer32 that is registered with the active region 30. The SAM 36 is overlaidwith a layer of functionalization (e.g., specific binding) material 38arranged to bind at least one analyte (e.g., analyte 42). Walls 44 thatare laterally displaced from the active region 30 extend upward from thehermeticity layer 32 to define lateral boundaries of the fluidic passage52 containing the active region 30. The cover or cap layer 46 defining afluidic inlet port 48 and a fluidic outlet port 50 is provided over thewalls 44 to provide an upper boundary for the fluidic passage 52.Operation of the fluidic device 58 of FIG. 4 is similar to the operationof the fluidic device 56 of FIG. 3. A volume of fluid may behave as a“stack” of horizontal fluid layers including a lowermost fluid layer 40Aand an uppermost fluid layer 40N within the fluidic passage 52, whereinthe lowermost fluid layer 40A is proximate to functionalization material38 overlying the active region 30. Assuming the presence of sufficientanalyte in the fluid (including the lowermost fluid layer 40A) when abulk acoustic wave having a dominant shear component is induced in theactive region 30 by supplying an electrical (e.g., alternating current)signal of a desired frequency to the bottom and top side electrodes 20,28, then a change in electroacoustic response of the BAW resonatorstructure may be detected to indicate a presence and/or quantity ofanalyte bound to the functionalization material 38.

FIG. 5 is a schematic cross-sectional view of a portion of a fluidicdevice 60 (e.g., a biochemical sensor device) that is similar to thefluidic device 58 of FIG. 4, but that includes an inlet port 62 arrangedabove an active region 30, and including two outlet ports 50A, 50B thatare laterally displaced from the active region 30. The fluidic device 60includes a fluidic passage 52 that is bounded from below by a bulkacoustic wave resonator structure including the active region 30,bounded laterally by lower wall-forming layer 43 and walls 44 (which maybe formed of stencil layers), and bounded from above by the cover or caplayer 46 defining the inlet port 62 and the outlet ports 50A, 50B. Thelower wall-forming layer 43 extends in a medial direction over ahermeticity layer 32, but does not cover the active region 30. Thefluidic device 60 includes a substrate 12 overlaid with an acousticreflector 14, and a bottom side electrode 20 arranged generally below(i.e., along a portion of a lower surface 24 of) the piezoelectricmaterial 22. The active region 30 is defined by a portion of thepiezoelectric material 22 arranged between a portion of a top sideelectrode 28 that overlaps the bottom side electrode 20. The hermeticitylayer 32 is arranged over the top side electrode 28 and thepiezoelectric material 22. An interface layer 34 and a SAM 36 areprovided over a portion of the hermeticity layer 32 that is registeredwith the active region 30. The SAM 36 is overlaid with a layer offunctionalization (e.g., specific binding) material 38 arranged to bindat least one analyte (e.g., analyte 42).

In use of the fluidic device 60, a fluid sample may be supplied throughthe inlet port 62 into the fluidic passage 52 over the active region 30to contact the functionalization material 38, and then flow through theoutlet ports 50A, 50B to exit the fluidic passage 52. The inlet port 62is arranged above and registered with the active region 30, and isthereby configured to supply fluid into the fluidic passage 52 in adirection substantially orthogonal to a surface of the active region 30.Such configuration causes fluid to initially flow downward toward asurface of the active region 30 (e.g., to impinge on functionalizationmaterial 38 overlying the active region 30) and then change direction toflow laterally through the fluidic passage 52 in a split stream. Thechange in direction of fluid within the fluidic passage 52 may promotemixing and/or reduce stratification of analyte within the fluidproximate to the active region 30, thereby permitting a rate of bindingbetween the analyte 42 and the functionalization material 38 to beincreased relative to the arrangement shown in FIGS. 3 and 4. Anincreased binding rate may reduce the time necessary to completemeasurement of a particular sample. When a bulk acoustic wave having adominant shear component is induced in the active region 30 by supplyingan electrical (e.g., alternating current) signal of a desired frequencyto the bottom and top side electrodes 20, 28, then a change inelectroacoustic response of the BAW resonator structure may be detectedto indicate a presence and/or quantity of analyte 42 bound to thefunctionalization material 38.

FIG. 6 is a schematic cross-sectional view of a portion of a fluidicdevice 64 (e.g., a biochemical sensor device) that is similar to thedevice 60 of FIG. 5, but that includes outlet ports 66A, 66B definedthrough a base structure (e.g., including a substrate 12, acousticreflector 14, and piezoelectric material 22 of a BAW resonatorstructure), and that includes only a single wall-forming layer (e.g.,walls) 44. An inlet port 62 is arranged over and registered with anactive region 30 of the BAW resonator structure, and is defined througha cover or cap layer 46 of the fluidic device 64. A fluidic passage 52is bounded from below by the BAW resonator structure, bounded laterallyby walls 44, and bounded from above by the cover or cap layer 46. Abottom side electrode 20 is arranged generally below (i.e., along aportion of a lower surface 24 of) the piezoelectric material 22. Theactive region 30 is defined by a portion of the piezoelectric material22 arranged between a portion of a top side electrode 28 that overlapsthe bottom side electrode 20. A hermeticity layer 32 is arranged overthe top side electrode 28 and the piezoelectric material 22. Aninterface layer 34 and a SAM 36 are provided over a portion of thehermeticity layer 32 that is registered with the active region 30. TheSAM 36 is overlaid with a layer of functionalization (e.g., specificbinding) material 38 arranged to bind at least one analyte (e.g.,analyte 42).

FIG. 11 is essentially the same as FIG. 6 except that the cover 46 andwalls 44 are shown as monolithic in FIG. 11. Reference is made to thediscussion above regarding FIG. 6 regarding the numerals used in FIG.11, as like parts or components are numbered the same.

In use of the fluidic device 64, a fluid sample may be supplied throughthe inlet port 62 into the fluidic passage 52 over the active region 30to contact the functionalization material 38, and then flow through theoutlet ports 66A, 66B to exit the fluidic passage 52. Arrangement of theinlet port 62 above and registered with the active region 30 causesfluid to be supplied into the fluidic passage 52 in a directionsubstantially orthogonal to a surface of the active region 30. Thiscauses fluid to initially flow downward toward a surface of the activeregion 30 (e.g., to impinge on functionalization material 38 overlyingthe active region 30) and then change direction to flow laterallythrough the fluidic passage 52 in a split stream. Such arrangement maypromote mixing and/or reduce stratification of analyte within the fluidproximate to the active region 30, thereby permitting a rate of bindingbetween analyte 42 and the functionalization material 38 to be increasedrelative to the arrangement shown in FIGS. 3 and 4. When a bulk acousticwave having a dominant shear component is induced in the active region30 by supplying an electrical (e.g., alternating current) signal of adesired frequency to the bottom and top side electrodes 20, 28, then achange in electroacoustic response of the BAW resonator structure may bedetected to indicate a presence and/or quantity of analyte 42 bound tothe functionalization material 38.

FIG. 7 is a schematic cross-sectional view of a portion of a fluidicdevice 68 (e.g., a biochemical sensor device) incorporating a BAWresonator structure and including inlet ports 62A-62C and at least someoutlet ports 50A-50D arranged over an active region 30 of the BAWresonator structure. The inlet ports 62A-62C and outlet ports 50A-50Dare defined in a cover or cap layer 46 that bounds a fluidic passage 52from above, with the fluidic passage 52 further being bounded from belowby a base structure including the BAW resonator structure, and beingbounded laterally by walls 44. The base structure includes a substrate12, an acoustic reflector 14, a piezoelectric material 22, a top sideelectrode 28, and a bottom side electrode 20. The bottom side electrode20 is arranged generally below (i.e., along a portion of a lower surface24 of) the piezoelectric material 22. The active region 30 is defined bya portion of the piezoelectric material 22 arranged between a portion ofthe top side electrode 28 that overlaps the bottom side electrode 20. Ahermeticity layer 32 is arranged over the top side electrode 28 and thepiezoelectric material 22. An interface layer 34 and a SAM 36 areprovided over a portion of the hermeticity layer 32 that is registeredwith the active region 30. The SAM 36 is overlaid with a layer offunctionalization (e.g., specific binding) material 38 arranged to bindat least one analyte (e.g., analyte 42).

In use of the fluidic device 68, a fluid sample may be supplied throughthe inlet ports 62A-62C into the fluidic passage 52 over the activeregion 30 to contact the functionalization material 38, and then flowthrough the outlet ports 50A-50D to exit the fluidic passage 52.Arrangement of the inlet ports 62A-62C above and registered with theactive region 30 causes fluid to be supplied into the fluidic passage 52in a direction substantially orthogonal to a surface of the activeregion 30. This causes fluid to initially flow downward toward a surfaceof the active region 30 (e.g., to impinge on functionalization material38 overlying the active region 30) and then change direction toultimately reverse direction and flow upward through the outlet ports50A-50D. Such arrangement may promote mixing and/or reducestratification of analyte within the fluid proximate to the activeregion 30, thereby permitting a rate of binding between analyte 42 andthe functionalization material 38 to be increased relative to thearrangement shown in FIGS. 3 and 4. When a bulk acoustic wave having adominant shear component is induced in the active region 30 by supplyingan electrical (e.g., alternating current) signal of a desired frequencyto the bottom and top side electrodes 20, 28, then a change inelectroacoustic response of the BAW resonator structure may be detectedto indicate a presence and/or quantity of analyte 42 bound to thefunctionalization material 38.

Although the preceding figures illustrate various solidly mounted bulkacoustic wave MEMS resonator structures, it is to be appreciated thatfilm bulk acoustic wave resonator (FBAR) structures may be employed influidic devices according to certain embodiments. FIG. 8A is a schematiccross-sectional view of a film bulk acoustic wave resonator (FBAR)structure 70 according to one embodiment including a layer of aninclined c-axis hexagonal crystal structure piezoelectric material 22.The FBAR structure 70 includes a substrate 72 (e.g., silicon or anothersemiconductor material) defining a cavity 74 optionally covered by asupport layer 76 (e.g., silicon dioxide), and includes an active region30 registered with the cavity 74, with a portion of the piezoelectricmaterial 22 arranged between overlapping portions of a top sideelectrode 28 and a bottom electrode 20. The bottom side electrode 20 isarranged over a portion of the support layer 76. The bottom sideelectrode 20 and the support layer 76 are overlaid with thepiezoelectric material 22 (e.g., embodying inclined c-axis hexagonalcrystal structure piezoelectric material such as AlN or ZnO), and thetop side electrode 28 is arranged over at least a portion of a topsurface of the piezoelectric material 22. A portion of the piezoelectricmaterial 22 arranged between the top side electrode 28 and the bottomside electrode 20 embodies the active region 30 of the FBAR structure70. The active region 30 is arranged over and registered with the cavity74 disposed below the support layer 76. The cavity 74 serves to confineacoustic waves induced in the active region 30 by preventing dissipationof acoustic energy into the substrate 72, since acoustic waves do notefficiently propagate across the cavity 74. In this respect, the cavity74 provides an alternative to the acoustic reflectors 14 illustrated anddescribed in connection with FIGS. 1 and 3-7. Although the cavity 74shown is bounded from below by a thinned portion of the substrate 72, inalternative embodiments at least a portion of the cavity 74 extendsthrough an entire thickness of the substrate 72. Steps for forming theFBAR structure 70 may include defining the cavity 74 in the substrate72, filling the cavity 74 with a sacrificial material (not shown),optionally followed by planarization of the sacrificial material,depositing the support layer 76 over the substrate 72 and thesacrificial material, removing the sacrificial material (e.g., byflowing an etchant through vertical openings defined in the substrate 72or the support layer 76, or lateral edges of the substrate 72),depositing the bottom side electrode 20 over the support layer 76,growing (e.g., via sputtering or other appropriate methods) thepiezoelectric material 22 and depositing the top side electrode 28. Incertain embodiments, the top side electrode 28, the piezoelectricmaterial 22, and the bottom side electrode 20 in combination may beself-supporting, and the support layer 76 may be omitted and/or removedby etching in the vicinity of the active region 30.

FIG. 8B is a schematic cross-sectional view of the FBAR structure 70 ofFIG. 8A with two outlet ports 66A, 66B defined through the FBARstructure 70 and laterally offset from the active region 30. In certainembodiments, the defining of the outlet ports 66A, 66B through thesubstrate 72 and the piezoelectric material 22 comprises lasermicromachining guided in a water jet. The outlet ports 66A, 66B arelaterally offset from the active region 30 as well as the cavity 74defined in the substrate 72.

FIG. 8C is a schematic cross-sectional view of a portion of a fluidicdevice 78 (e.g., a biochemical sensor device) including a fluidicpassage 52 bounded from below by the FBAR structure 70 of FIG. 8B,bounded laterally by walls 44, and bounded from above by a cover or caplayer 46 defining an inlet port 62 that is centrally arranged above theactive region 30 of the FBAR structure 70. A hermeticity layer 32 isarranged over the top side electrode 28 and the piezoelectric material22. An interface layer 34 and a SAM 36 are provided over a portion ofthe hermeticity layer 32 that is registered with the active region 30.The SAM 36 is overlaid with functionalization (e.g., specific binding)material 38. As shown in FIG. 8C, an analyte 42 supplied by the fluidsample is bound to the functionalization material 38. The fluidic device78 may be used as a sensor to detect presence of a target species in anenvironment. When a bulk acoustic wave is induced in the active region30 by supplying an electrical signal (e.g., a radio frequencyalternating current signal configured to drive the piezoelectricmaterial 22 in a shear mode) to the bottom and top side electrodes 20,28, detection of a change in at least one of an amplitude-magnitudeproperty, a frequency property, or a phase property of the FBARstructure 70 indicates a presence and/or quantity of target species(i.e., analyte 42) bound to the functionalization material 38.

In use of the fluidic device 78, a fluid sample may be supplied throughthe inlet port 62 into the fluidic passage 52 over the active region 30,and then flow through the outlet ports 66A, 66B to exit the fluidicpassage 52. Being arranged above and registered with the active region30, the inlet port 62 is configured to supply fluid in a directionsubstantially orthogonal to a surface of the active region 30, therebypromoting mixing and/or reducing stratification of analyte within thefluid proximate to the active region 30.

FIG. 9 is a top plan view photograph of a bulk acoustic wave MEMSresonator device 10 (consistent with the portion of the resonator device10 illustrated in FIG. 1) suitable for receiving a hermeticity layer, aninterface layer, a self-assembled monolayer, and/or functionalization(e.g., specific binding) material as disclosed herein. The MEMSresonator device 10 includes a piezoelectric material (not shown)arranged over a substrate 12, a bottom side electrode 20 arranged undera portion of the piezoelectric material, and a top side electrode 28arranged over a portion of the piezoelectric material, including anactive region 30 in which the piezoelectric material is arranged betweenoverlapping portions of the top side electrode 28 and the bottom sideelectrode 20. Externally accessible contacts 20A, 28A are in electricalcommunication with the bottom side electrode 20 and the top sideelectrode 28, respectively. After portions of the resonator device 10are overlaid with an interface layer, a self-assembled monolayer, andfunctionalization (e.g., specific binding) material as disclosed herein,the resonator device 10 may be used as a sensor and/or incorporated intoa microfluidic device. If desired, multiple resonator devices 10 may beprovided in an array on a single substrate 12.

FIG. 10 is a perspective assembly view of a microfluidic device 100incorporating a substrate 102 with multiple bulk acoustic wave MEMSresonator structures, an intermediate layer 120 defining a centralmicrofluidic channel 122 registered with active regions 108A-108D of theMEMS resonator structures, and a cover or cap layer 131 arranged tocover the intermediate layer 120. The substrate 102 preferably includesan acoustic reflector (not shown) and a piezoelectric material (notshown). Top central portions of the substrate 102 include a top sideelectrode 106 and bottom side electrodes 104A-104D. Regions in which theforegoing electrodes overlap one another and sandwich the piezoelectricmaterial embody active regions 108A-108D. Preferably, the active regions108A-108D are overlaid with a hermeticity layer, an interface layer, aself-assembled monolayer, and functionalization (e.g., specific binding)material as disclosed herein. Any suitable number of active regions108A-108D may be provided and fluidically arranged in series orparallel, although four active regions are illustrated in FIG. 10. Topperipheral (or top end) portions of the substrate 102 further includereference top side electrodes 116 and reference bottom side electrodes114 in communication with reference overlap regions 110. Such referenceoverlap regions 110 are not exposed to fluid, and are present to providea basis for comparing signals obtained from the active regions 108A-108Dexposed to fluid within the central microfluidic channel 122.

The substrate 102 is overlaid with the intermediate (e.g.,wall-defining) layer 120, wherein the central microfluidic channel 122is intended to receive fluid, and defines peripheral chambers 124arranged to overlie the reference overlap regions 110 in a sealedfashion. The intermediate layer 120 may be formed of any suitablematerial such as SU-8 negative epoxy resist, other photoresist material,or laser-cut “stencil” layers of thin polymeric materials optionallyincluding one or more self-adhesive surfaces (e.g., adhesive tape), etc.The intermediate layer 120 further includes a lateral inset region 126that enables lateral portions of the top side electrode 106 and bottomside electrodes 104A-104D to be accessed upon assembly of themicrofluidic device 100.

The cover or cap layer 131 includes a lateral inset region 136registered with the lateral inset region 126 of the intermediate layer120. The cover or cap layer 131 further defines microfluidic inlet ports132A-132D and microfluidic outlet ports 130A, 130B that are accessiblealong a top surface 138 of the cover or cap layer 131. The inlet ports132A-132D are configured to be arranged over and registered with theactive regions 108A-108D, whereas the outlet ports 130A, 130B arelaterally offset from the active regions 108A-108D and are registeredwith end portions of the central microfluidic channel 122 defined in theintermediate layer 120. The inlet ports 132A-132D permit fluid (e.g.,liquid) to be supplied to the central microfluidic channel 122 over theactive regions 108A-108D, with each inlet port 132A-132D beingregistered with a different active region 108A-108D to permit fluid tobe supplied in a direction substantially orthogonal to a surface of eachactive region 108-108D. Fluid is then transported through the centralmicrofluidic channel 122 to the outlet ports 130A, 130B. Microfluidicdevices according to other configurations may be provided, as will berecognized by those skilled in the art upon review of the presentdisclosure.

Technical benefits obtainable with various embodiments of the presentdisclosure may include one or more of the following: enhanced rate ofanalyte binding to functionalization material overlying an active regionof a bulk acoustic wave resonator structure, thereby reducing the timerequired to complete measurement of a particular sample, and/or enhancedmixing of analyte-containing fluids in fluidic devices incorporatingbulk acoustic wave resonator structures, including devices suitable forbiosensing or biochemical sensing applications.

Those skilled in the art will recognize improvements and modificationsto the preferred embodiments of the present disclosure. All suchimprovements and modifications are considered within the scope of theconcepts disclosed herein and the claims that follow.

What is claimed is:
 1. A method for biological or chemical sensing, themethod comprising: supplying a fluid containing a target species to afluidic device including a fluidic passage containing an active regionof at least one bulk acoustic wave resonator structure, wherein at leasta portion of the active region is overlaid with at least onefunctionalization material, wherein said supplying is configured tointroduce the fluid through at least one first port registered with theactive region to cause the fluid to enter the fluidic passage in a firstdirection normal to a planar surface of the active region and to causeat least some of the target species to bind to the at least onefunctionalization material; inducing a bulk acoustic wave in the activeregion; and sensing a change in at least one of an amplitude-magnitudeproperty, a frequency property, or a phase property of the at least onebulk acoustic wave resonator structure to indicate at least one ofpresence or quantity of target species bound to the at least onefunctionalization material.
 2. The method of claim 1, wherein thefluidic passage is in fluid communication with at least one second portthat is laterally displaced relative to the at least one first port, andwherein said supplying is further configured to cause at least a portionof the fluid to transit through the fluidic passage in a lateraldirection and thereafter exit the fluidic passage through the at leastone second port.
 3. The method of claim 1, wherein: the at least onebulk acoustic wave resonator structure includes a top side electrode, apiezoelectric material, and a bottom side electrode arranged over asubstrate; the piezoelectric material comprises a c-axis having anorientation distribution that is predominantly non-parallel to normal ofa face of the substrate; a portion of the piezoelectric material isarranged between the top side electrode and the bottom side electrode toform the active region; and the inducing of a bulk acoustic wave in theactive region comprises applying an alternating current signal acrossthe top side electrode and the bottom side electrode, whereby the atleast one bulk acoustic wave resonator structure exhibits a dominantshear response upon application of the alternating current signal.
 4. Amethod for identifying a target species, the method comprising:supplying a fluid containing the target species to a fluidic devicecomprising a fluidic passage containing an active region of at least onebulk acoustic wave resonator structure, wherein at least a portion ofthe active region is overlaid with at least one functionalizationmaterial, wherein said supplying is configured to introduce the fluidthrough at least one first port registered with the active region tocause the fluid to enter the fluidic passage in a first direction normalto a planar surface of the active region and to cause at least some ofthe target species to bind to the at least one functionalizationmaterial; inducing a bulk acoustic wave in the active region; andsensing a change in at least one of an amplitude-magnitude property, afrequency property, or a phase property of the at least one bulkacoustic wave resonator structure to indicate at least one of a presenceor a quantity of the target species bound to the at least onefunctionalization material.
 5. The method of claim 4, wherein thefluidic passage is in fluid communication with at least one second portthat is laterally displaced relative to the at least one first port, andwherein said supplying is further configured to cause at least a portionof the fluid to transit through the fluidic passage in a lateraldirection and thereafter exit the fluidic passage through the at leastone second port.
 6. The method of claim 4, wherein: the at least onebulk acoustic wave resonator structure comprises a top side electrode, apiezoelectric material, and a bottom side electrode arranged over asubstrate; the piezoelectric material comprises a c-axis having anorientation distribution that is predominantly non-parallel to normal ofa face of the substrate; a portion of the piezoelectric material isarranged between the top side electrode and the bottom side electrode toform the active region; and inducing the bulk acoustic wave in theactive region comprises applying an alternating current signal acrossthe top side electrode and the bottom side electrode, whereby the atleast one bulk acoustic wave resonator structure exhibits a dominantshear response upon application of the alternating current signal.
 7. Amethod for supplying a fluid sample through a fluidic device, the methodcomprising: providing the fluid sample comprising a target speciesthrough an inlet port of the fluidic device, wherein the fluidic devicecomprises a fluidic passage containing an active region of at least onebulk acoustic wave resonator structure; the active region is overlaidwith at least one functionalization material; and the inlet port isdefined above and registered with the active region to cause the fluidsample to enter the fluidic passage in a first direction normal to aplanar surface of the active region; mixing the fluid sample proximateto the active region to reduce stratification of the target specieswithin the fluid sample; flowing the mixed fluid sample over the activeregion in the fluidic passage; contacting the mixed fluid sample withthe functionalization material; and flowing the mixed fluid sample outof the fluidic passage through at least one outlet port.
 8. The methodof claim 7, wherein contacting the mixed fluid sample with thefunctionalization material comprises binding the target species to asurface of the functionalization material.
 9. The method of claim 7,wherein the at least one outlet port is defined in a cover structure ofthe fluidic device, the cover structure forming an upper boundary of thefluidic passage.
 10. The method of claim 7, wherein the at least oneoutlet port is defined in a base structure of the fluidic device, thebase structure comprising: (i) a substrate; (ii) the at least one bulkacoustic wave resonator structure supported by the substrate; and (iii)the at least one functionalization material arranged over at least aportion of the active region.
 11. The method of claim 10, wherein thesubstrate defines a recess arranged below the active region.
 12. Themethod of claim 7, wherein the at least one bulk acoustic wave resonatorstructure includes a top side electrode, a piezoelectric material, and abottom side electrode arranged over a substrate; and a portion of thepiezoelectric material is arranged between the top side electrode andthe bottom side electrode to form the active region.
 13. A method fordetecting a target species, the method comprising: providing a fluidsample comprising the target species through an inlet port of a fluidicdevice, wherein the fluidic device comprises a fluidic passagecontaining an active region of at least one bulk acoustic wave resonatorstructure; the active region is overlaid with at least onefunctionalization material; and the inlet port is defined above andregistered with the active region to cause the fluid sample to enter thefluidic passage in a first direction normal to a planar surface of theactive region; mixing the fluid sample proximate the active region toreduce stratification of the target species within the fluid sample;flowing the mixed fluid sample over the active region in the fluidicpassage; contacting the mixed fluid sample with the functionalizationmaterial; and flowing the mixed fluid sample out of the fluidic passagethrough at least one outlet port.
 14. The method of claim 13, whereincontacting the mixed fluid sample with the functionalization materialcomprises binding at least a portion of the target species to a surfaceof the functionalization material.
 15. The method of claim 14, furthercomprising: inducing a bulk acoustic wave in the active region; anddetecting a change in a property of the at least one bulk acoustic waveresonator structure to indicate at least one of a presence or a quantityof the target species bound to the at least one functionalizationmaterial.
 16. The method of claim 15, wherein the property of the atleast one bulk acoustic wave resonator comprises an amplitude-magnitudeproperty, a frequency property, or a phase property.
 17. The method ofclaim 15, wherein the at least one bulk acoustic wave resonatorstructure includes a top side electrode, a piezoelectric material, and abottom side electrode arranged over a substrate; and a portion of thepiezoelectric material is arranged between the top side electrode andthe bottom side electrode to form the active region.
 18. The method ofclaim 17, wherein inducing the bulk acoustic wave in the active regioncomprises applying an electrical signal across the top side electrodeand the bottom side electrode, whereby the at least one bulk acousticwave resonator structure exhibits a dominant shear response uponapplication of the electrical signal.
 19. The method of claim 13,wherein the at least one bulk acoustic wave resonator structure includesa top side electrode, a piezoelectric material, and a bottom sideelectrode arranged over a substrate; and a portion of the piezoelectricmaterial is arranged between the top side electrode and the bottom sideelectrode to form the active region.
 20. The method of claim 19, whereinthe piezoelectric material comprises a c-axis having an orientationdistribution that is predominantly non-parallel to normal of a face ofthe substrate.